Investigators are being undertaken to define the role of receptors on the presynaptic membrane to modulate norepinephrine release in a densely innervated muscular artery in normotensive rats. Transmitter release modulation is evaluated under conditions of differing levels of neurogenic vasoconstrictor tone which is elicited by physiologic stress. The level of neurogenic vasomotor tone is estimated by measuring the activities of the rate-limiting enzymes in the biosynthesis of the neurotransmitter. Angiotension, beta and alpha-two receptors on the presynaptic membrane are being investigated before and following chronic but physiologic elevations or depressions of sympathetic vasomotor nerve activity. Quantitative measures of norepinephrine release following transmural nerve stimulation are being correlated with the level of nerve activity while under the influence of various agents which modulate transmitter release via an action on the presynaptic membrane. These studies will be extended to several models of experimental hypertension. Physiological stress will be applied to hypertensive rats to alter the sympathetic vascular tone. The action of presynaptically acting modulators of neurotransmitter release will be evaluated and compared with the changes noted in normotensive animals. An attempt will be made to determine whether changes in presynaptic modulation of norepinephrine release are minimized or exaggerated by the hypertensive state.